Cryptococcus neoformans is one of the most serious fungal pathogens affecting primarily immunocompromised individuals such as those with AIDS. It is a unicellular budding yeast which is surrounded by a thick polysaccharide capsule. The fungus is neurotropic and causes meningoencephalitis which is fatal unless treated. In the past 7 years, our laboratory has made considerable progress in the identification of genes associated with pathogenicity and virulence of C. neoformans. During 1993- 1999, four capsule genes have been identified and characterized as essential for virulence of the organism. During the past 2 years we have focused on the molecular dissections of the mating type specific genes that regulate the expression of virulence associated genes such as the CAP genes. In order to accomplish this purpose, we first identified and mapped the boundary of the alpha mating type alpha locus and detected three MAP kinase cascade genes such as the STE11alpha, STE20alpha, and STE12alpha within the locus and cloned two additional mating type alpha specific genes, CPR1alpha and Myosine. The STE12alpha/a genes were found to regulate the expression of virulence associated genes such as capsule genes. Interestingly,a null mutant of pheromone receptor also exhibited a significant decrease in capsule formation and virulence of C. neoformans